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Generation of high-yield insulin producing cells from human bone marrow mesenchymal stem cells

Molecular Biology Reports volume 41, pages 4783–4794 (2014)Cite this article

Abstract

Allogenic islet transplantation is a most efficient approach for treatment of diabetes mellitus. However, the scarcity of islets and long term need for an immunosuppressant limits its application. Recently, cell replacement therapies that generate of unlimited sources of β cells have been developed to overcome these limitations. In this study we have described a stage specific differentiation protocol for the generation of insulin producing islet-like clusters from human bone marrow mesenchymal stem cells (hBM-MSCs). This specific stepwise protocol induced differentiation of hMSCs into definitive endoderm, pancreatic endoderm and pancreatic endocrine cells that expressed of sox17, foxa2, pdx1, ngn3, nkx2.2, insulin, glucagon, somatostatin, pancreatic polypeptide, and glut2 transcripts respectively. In addition, immunocytochemical analysis confirmed protein expression of the above mentioned genes. Western blot analysis discriminated insulin from proinsulin in the final differentiated cells. In derived insulin producing cells (IPCs), secreted insulin and C-peptide was in a glucose dependent manner. We have developed a protocol that generates effective high-yield human IPCs from hBM-MSCs in vitro. These finding suggest that functional IPCs generated by this procedure can be used as a cell-based approach for insulin dependent diabetes mellitus.

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Acknowledgments

The authors would like to thank the Iranian National Science Foundation (INSF) for supporting this project under contract no: 90006892.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Arefeh Jafarian & Mohammad Taghikhani

  2. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115 111, Tehran, Iran

    Saeid Abroun, Amir Allahverdi & Masoud Soleimani

  3. Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Zahra Pourpak

Authors
  1. Arefeh Jafarian
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  2. Mohammad Taghikhani
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  3. Saeid Abroun
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  4. Zahra Pourpak
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  5. Amir Allahverdi
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  6. Masoud Soleimani
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Corresponding authors

Correspondence to Mohammad Taghikhani or Masoud Soleimani.

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Jafarian, A., Taghikhani, M., Abroun, S. et al. Generation of high-yield insulin producing cells from human bone marrow mesenchymal stem cells. Mol Biol Rep 41, 4783–4794 (2014). https://doi.org/10.1007/s11033-014-3349-5

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  • DOI: https://doi.org/10.1007/s11033-014-3349-5

Keywords

  • Diabetes mellitus
  • Mesenchymal stem cells
  • Differentiation
  • Insulin producing cells
  • Transcription factors